miroliverELAP for Acute Liver Failure

Recruiting at 9 trial locations

Overseen By M. Mason Macenski, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Miromatrix Medical Inc.

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 48 hours

15 Participants Needed

Trial Summary

What is the purpose of this trial?

The clinical trail will assess the safety of miroliverELAP for the treatment of acute liver failure without underlying chronic liver disease. miroliverELAP is an external liver assist combination product consisting of a single-use MIRO-001 bioengineered liver graft and an extracorporeal blood circuit. miroliverELAP Is intended to support the native (failed) liver for up to 48-hours of continuous treatment to allow time for liver recovery or to identify a transplantable liver.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are on medications with a narrow therapeutic index.

What data supports the idea that miroliverELAP for Acute Liver Failure is an effective treatment?

The available research shows that miroliverELAP, a bioengineered liver graft, can effectively support a failing liver in cases of Acute Liver Failure. In animal models, these grafts performed important liver functions like producing albumin and detoxifying harmful substances, similar to a normal liver. The study also demonstrated that these grafts provided long-term survival and function, suggesting they could be a potential bridge to liver transplantation. Compared to other treatments, miroliverELAP offers a promising alternative due to its ability to provide natural biological support and long-term effectiveness. ^{1 2 3 4 5}

What safety data is available for miroliverELAP in treating acute liver failure?

The provided research does not contain specific safety data for miroliverELAP, miroliverELAP, or MIRO-001 bioengineered liver graft. The studies focus on other treatments and procedures for acute liver failure, such as plasma exchange, steroids, and living donor liver transplantation. ^{6 7 8 9 10}

Is the treatment miroliverELAP a promising treatment for acute liver failure?

Yes, miroliverELAP is a promising treatment for acute liver failure. It is a type of bioengineered liver graft that can help patients by acting as a temporary liver support. This treatment can bridge patients to a liver transplant or help their liver recover. Studies have shown that similar bioartificial liver systems have been safe and effective in improving liver function and supporting patients until they receive a transplant. ^{2 4 11 12 13}

Research Team

Jack Lake, MD

Principal Investigator

Miromatrix

Eligibility Criteria

This trial is for individuals with sudden severe liver failure not caused by long-term liver disease. Participants must be in need of support while their own liver recovers or until a transplant is available.

Inclusion Criteria

I am able to understand and agree to the study, or I have someone legally authorized to consent for me.

I am between 8 and 80 years old.

I am not eligible for a liver transplant now or if my condition worsens.

Exclusion Criteria

Underlying chronic liver disease including acute-on-chronic liver disease, acute alcoholic-associated hepatitis, cirrhosis, Grade IV West Haven Encephalopathy Criteria, previous liver transplant, currently requires chronic hemodialysis, uncontrolled documented infection, hypotension or refractory shock, liver injury due to trauma, any current liver cancer, currently on medications with a narrow therapeutic index, platelet count < 40,000 μL, subject is intubated and has an acute lung injury, experiencing a bleeding event defined as active gastrointestinal or other overt bleeding event, hemoglobin drop > 3g/dL within the past 24 hours, received ≥ 3 units of red blood cell transfusion within the past 24 hours, female that is currently pregnant, planning to be pregnant, or currently breastfeeding, refusal to receive blood products

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive continuous treatment with miroliverELAP for 48 hours

48 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

32 days

Treatment Details

Interventions

• miroliverELAP

Trial Overview The safety of miroliverELAP, an external device designed to assist the failing liver, is being tested. It combines a bioengineered liver graft and blood circuit to support patients for up to 48 hours.

Participant Groups

Group I: miroliverELAP treatment Experimental Treatment 1 Intervention

48 hour treatment with miroliverELAP

Who Is Running the Clinical Trial?

Miromatrix Medical Inc.

Lead Sponsor

Trials

6

Recruited

200+

Findings from Research

This study presents a novel approach to creating transplantable humanized liver grafts that can provide long-term support for acute liver failure (ALF) in animal models, addressing the limitations of current liver transplantation methods.

The bioengineered liver grafts demonstrated essential liver functions, such as albumin production and urea synthesis, comparable to normal liver, suggesting they could serve as a viable temporary solution while waiting for a donor organ.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal transplantation of bioengineered humanized liver grafts supports failing liver in acute condition. Vishwakarma, SK., Bardia, A., Lakkireddy, C., et al.[2019]

The study successfully developed bioengineered liver (BEL) grafts using decellularized porcine liver scaffolds entirely seeded with human cells, which adhered to safety guidelines and showed improved functionality compared to grafts seeded with porcine cells.

BELs seeded with primary human liver cells (PHLCs) were more effective at clearing ammonia and maintained their function after cold storage, indicating their potential as a bridge therapy for patients with acute liver failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure. Nelson, VL., Stumbras, AR., Palumbo, RN., et al.[2023]

Hybrid bioartificial liver (BAL) support systems are being developed as a treatment for acute liver failure, as fully artificial systems have not been effective; current BAL devices are still in early stages of development.

Hollow-fiber bioreactors show the most promise for BAL devices, which aim to support patients until a liver transplant can be performed, although the risks associated with using animal-derived components are still not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extracorporeal tissue engineered liver-assist devices. Tzanakakis, ES., Hess, DJ., Sielaff, TD., et al.[2006]

The bioartificial liver support system, using porcine hepatocytes, was tested on seven patients with severe acute liver failure and was found to be safe, with all patients tolerating the procedure well and surviving to receive liver transplants.

Patients showed significant improvements in neurological function, decreased intracranial pressure, and reduced plasma ammonia levels, indicating the system's efficacy in providing metabolic support during the critical period before transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A bioartificial liver to treat severe acute liver failure. Rozga, J., Podesta, L., LePage, E., et al.[2019]

The TECA-I bioartificial liver support system (BALSS) significantly improved survival and reduced harmful plasma levels in canines with acute liver failure (ALF) after 80% liver resection, with an average survival time of 108 hours compared to only 24 hours in the control group.

BALSS treatment led to beneficial changes in liver function markers, such as decreased plasma ammonia and liver enzymes, while showing no adverse effects on immune parameters, indicating its safety and efficacy in treating ALF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental research on TECA-I bioartificial liver support system to treat canines with acute liver failure. Chen, XP., Xue, YL., Li, XJ., et al.[2019]

In a study of 94 adult-to-adult living donor liver transplantations (AALDLT), the donor complication rate was low at 7.4%, indicating a safe surgical protocol for donors aged 19 to 60 years.

The 1-year survival rate for patients was high at 95.7%, demonstrating the efficacy of AALDLT as a treatment for end-stage liver disease, regardless of the type of liver graft used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adult-to-adult living donor liver transplantation with 94 cases report]. Zhu, ZJ., Zhu, LW., Gao, W., et al.[2012]

Timely adult-to-adult living-donor liver transplantation (AALDLT) significantly improves survival rates for patients with acute liver failure (ALF), with a 1-year survival rate of 65% among recipients.

Waiting longer than 5 days for transplantation is associated with increased mortality and worse renal function in recipients, highlighting the importance of prompt intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adult-to-adult living donor liver transplantation for acute liver failure in China. Yuan, D., Liu, F., Wei, YG., et al.[2021]

In a study of 22 patients with idiosyncratic drug-induced liver injury (iDILI) who underwent low-volume plasma exchange (PLEX-LV) and low-dose steroids, 59% achieved one-month transplant-free survival, indicating this treatment may be effective for patients not opting for liver transplantation.

A significant predictor of improved survival was a reduction of 25% or more in plasma von Willebrand factor (VWF) levels after PLEX-LV, suggesting that monitoring VWF could help assess treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Centre Experience With Low-Volume Plasma Exchange and Low-Dose Steroid to Treat Patients With Idiosyncratic Drug-Induced Acute Liver Failure. Singh, KA., Kumar, SE., Zachariah, UG., et al.[2023]

A study of 50 adult-to-adult living donor liver transplantations (A-A LDLT) showed that when the remnant liver volume of donors is over 35% and the graft volume to recipient standard liver volume ratio exceeds 40%, the procedure is very safe for both donors and recipients.

The 1-year survival rate for recipients was 92%, with a low donor mortality rate and manageable complication rates, indicating that A-A LDLT can be an effective treatment option for patients with severe liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical study on safety of adult-to-adult living donor liver transplantation in both donors and recipients. Liu, B., Yan, LN., Wang, WT., et al.[2019]

A study involving 70 patients who underwent adult-to-adult right-lobe living donor liver transplantation (ARL-LDLT) showed that it is a safe and effective option for patients with high MELD scores suffering from HBV-related benign liver disease.

Short-term outcomes, such as 30-day mortality and graft loss, were similar between ARL-LDLT and deceased donor liver transplantation (DDLT), indicating that high MELD scores do not necessarily prevent successful transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adult-to-adult right-lobe living donor liver transplantation in recipients with hepatitis B virus-related benign liver disease and high model end-stage liver disease scores. Jiang, L., Yan, L., Tan, Y., et al.[2021]

The AMC-bio-artificial liver (BAL) system was tested in a phase I study involving 7 patients with acute liver failure, demonstrating safety with no severe adverse events reported during treatment.

Out of the 7 patients, 6 were successfully bridged to liver transplantation, and one patient improved enough to avoid the need for a transplant, indicating the potential efficacy of the AMC-BAL system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical trial with the AMC-bioartificial liver. van de Kerkhove, MP., Di Florio, E., Scuderi, V., et al.[2019]

Liver transplantation is currently the only definitive treatment for liver failure, but it is limited by organ shortages, high costs, and the need for specialized expertise, leaving many patients without options.

Alternative cell-based liver therapies, such as bioartificial livers, liver cell injections, and tissue engineering, show promise in expanding treatment availability and improving liver function, despite facing significant challenges in research and clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver cell therapy and tissue engineering for transplantation. Vacanti, JP., Kulig, KM.[2022]

In a study involving healthy pigs with drug-overdose acute liver failure, the spheroid reservoir bioartificial liver (SRBAL) significantly improved survival rates to 83% compared to 0% for standard therapy alone and 17% for a no-cell device, highlighting its potential efficacy in treating liver failure.

The SRBAL's effectiveness was linked to its ability to detoxify ammonia and reduce intracranial pressure, suggesting that the hepatocyte spheroids within the device can prevent severe brain complications associated with acute liver failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pivotal preclinical trial of the spheroid reservoir bioartificial liver. Glorioso, JM., Mao, SA., Rodysill, B., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Intraperitoneal transplantation of bioengineered humanized liver grafts supports failing liver in acute condition. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Extracorporeal tissue engineered liver-assist devices. [2006]

4. United States pubmed.ncbi.nlm.nih.gov

A bioartificial liver to treat severe acute liver failure. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Experimental research on TECA-I bioartificial liver support system to treat canines with acute liver failure. [2019]

6. China pubmed.ncbi.nlm.nih.gov

[Adult-to-adult living donor liver transplantation with 94 cases report]. [2012]

7. United States pubmed.ncbi.nlm.nih.gov

Adult-to-adult living donor liver transplantation for acute liver failure in China. [2021]

8. India pubmed.ncbi.nlm.nih.gov

Single-Centre Experience With Low-Volume Plasma Exchange and Low-Dose Steroid to Treat Patients With Idiosyncratic Drug-Induced Acute Liver Failure. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Clinical study on safety of adult-to-adult living donor liver transplantation in both donors and recipients. [2019]

10. Japan pubmed.ncbi.nlm.nih.gov

Adult-to-adult right-lobe living donor liver transplantation in recipients with hepatitis B virus-related benign liver disease and high model end-stage liver disease scores. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Phase I clinical trial with the AMC-bioartificial liver. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Liver cell therapy and tissue engineering for transplantation. [2022]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Pivotal preclinical trial of the spheroid reservoir bioartificial liver. [2022]